HES1、JAG1、MT2A和MAFA介导茶多酚抑制微卫星不稳定结直肠癌  

Tea polyphenol inhibits colorectal cancer with microsatellite instability by regulating the expressions of HES1,JAG1,MT2A and MAFA

作　　者：许妍妍[1] 金黑鹰[1] 谈瑄忠[1] 刘秀芳[1] 丁义江[1] 

机构地区：[1]南京中医药大学第三附属医院全国肛肠医疗中心,江苏南京210001

出　　处：《中西医结合学报》2010年第9期870-876,共7页Journal of Chinese Integrative Medicine

基　　金：国家自然科学基金资助课题(No.30572447;No.30979837);南京市医学发展重点项目资助课题(No.ZKX05028);江苏省自然科学基金资助课题(No.BK2007009)

摘　　要：目的:探讨茶多酚是否能特异性抑制结直肠癌微卫星不稳定及其可能机制。方法:使用茶多酚的水溶液处理LoVo细胞(MSH2基因缺失的结肠癌细胞株)和SW480细胞(错配修复基因正常的结肠癌细胞株),四甲基偶氮唑盐法检测细胞增殖,基因扫描法检测细胞的微卫星序列变化,基因芯片检测茶多酚处理后LoVo细胞基因表达的变化,实时荧光定量聚合酶链式反应(polymerase chain reaction,PCR)检测有变化的基因。结果:茶多酚对LoVo细胞和SW480细胞的抑制率随着药物浓度的增加而增加,随着时间的延长也呈逐渐上升趋势,但茶多酚对LoVo细胞的抑制率高于SW480细胞,在24、72h和1周时间点测得二者抑制率的差异有统计学意义。经过茶多酚处理后,LoVo细胞的微卫星序列有趋于稳定的趋势。基因芯片和实时荧光定量PCR检测结果提示茶多酚能抑制MT2A、MAFA、HES1和JAG1基因的表达,治疗前后基因表达差异均有统计学意义。结肠癌相关基因检查发现,茶多酚能上调BAX和抑制P38基因,治疗前后基因表达差异有统计学意义,但是对于核因子-κB抑制不明显。结论:茶多酚有使LoVo的微卫星状态趋于稳定的趋势,并可抑制MT2A、MAFA、HES1和JAG1等基因表达,同时上调BAX基因的表达和抑制P38基因的表达;但是对于这些途径怎么相互联系,哪些是始动原因,哪些是继发性原因还需要进一步研究。Objective:To investigate the mechanism of tea polyphenol in inhibiting microsatellite instability (MSI) of colorectal cancer.Methods:Using LoVo cells and SW480 cells treated with aqueous solution of tea polyphenol,cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) method,changes in microsatellite sequences were detected by genescan method and changes in gene expression of LoVo cells were detected by illumina expression arrays and quantitative real-time polymerase chain reaction (PCR).Results:The proliferation inhibition rates of LoVo and SW480 cells treated with tea polyphenol increased with the increasing of drug concentration and showed an increasing tendency with time. The proliferation inhibition rate of LoVo cells with tea polyphenol was higher than that of SW480 cells,and there was a significant difference in the proliferation inhibition rates at 24 h,72 h and one week. The microsatellite sequence of LoVo cells treated with tea polyphenol remained stable. The gene expression arrays and quantitative real-time PCR suggested that tea polyphenol inhibited the gene expressions of MT2A,MAFA,HES1 and JAG1 nearly two-fold over controls. It was also found that tea polyphenol inhibited the BAX and p38 genes with a more than two-fold difference but did not significantly inhibit the nuclear factor-κB pathway.Conclusion:Tea polyphenol significantly inhibited the proliferation of MSI colorectal cancer cells and stably maintained the microsatellite state in MSI colorectal cancer. Tea polyphenol inhibited the gene expressions of HES1,JAG1,MT2A and MAFA,up-regulated the gene expression of BAX and down-regulated that of P38. Further research is required to investigate how these pathways are interrelated.

关 键 词：茶多酚 结直肠癌 微卫星不稳定 基因表达 

分 类 号：R735.3[医药卫生—肿瘤]